The human colon is colonised with a wide range of bacteria that have both positive and negative effects on gut physiology as well as having other systemic influences. Predominant groups of bacteria found in the colon include bacteroides, bifidobacteria, eubacteria, clostridia and lactobacilli. The bacteria present have fluctuating activities in response to substrate availability, redox potential, pH, O2 tension and distribution in the colon. In general intestinal bacteria can be divided into species that may potentially exert either harmful or beneficial effects on the host. Pathogenic effects (which may be caused by clostridia or bacteroides, for example) include diarrhoea, infections, liver damage, carcinogenesis and intestinal putrefaction. Health-promoting effects may be caused by the inhibition of growth of, and colonisation by, harmful bacteria, stimulation of immune functions, improving digestion and absorption of essential nutrients and synthesis of vitamins. An increase in the numbers and/or activities of bacterial species such as Bifidobacterium and Lactobacillus that may have health promoting properties is desirable.
In the recent past, certain strains of bacteria have attracted considerable attention because they have been found to exhibit valuable properties for man if ingested. In particular, specific strains of the genera Lactobacilli and Bifidobacteria have been found to be able to colonise at least transiently the intestinal mucosa, to reduce the capability of pathogenic bacteria to adhere to the intestinal epithelium, to have immunomodulatory effects and to assist in the maintenance of well-being. Such bacteria are commonly called probiotics.
Extensive studies have been carried out to identify new probiotic strains. For example, EP 0 199 535, EP 0 768 375, WO 9700078, EP 0 577 903 and WO 0053200 disclose specific strains of lactobacilli and bifidobacteria and their beneficial effects.
A probiotic may be defined as a live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance. Certain strains of Lactobacilli and Bifidobacteria such as, for example, Lactobacillus paracasei CNCM 1-2116, Lactobacillus rhamnosus ATCC 53103, Bifidobacterium lactis BB12®, Bifidobacterium longum ATCC BAA-999, Lactobacillus reuteri ATCC 55730 and Bifidobacterium breve M-16V® have been demonstrated to have these properties. Such probiotic lactobacilli and bifidobacteria are commonly added to human foods, such as fermented milk products. It is known that probiotics generally have a prophylactic and therapeutic effect on pathogenic infections of the gastrointestinal tract such as those caused by Clostridia and Salmonella species for example. In EP 904 784 it is proposed to use a combination of three different types of probiotic for the treatment of gastrointestinal disorders. More recently, it has been suggested that some probiotic strains may also be effective in the prevention and treatment of infections of the upper respiratory tract (British Medical Journal 2001, 322:1-5).
As far as infants specifically are concerned, immediately before birth, the gastro-intestinal tract of a baby is thought to be sterile. During the process of birth, it encounters bacteria from the digestive tract and skin of the mother and starts to become colonised. Large differences exist with respect to the composition of the gut microbiota in response to the infant's feeding. The faecal flora of breast-fed infants includes appreciable populations of bifidobacteria with some lactobacilli, whereas formula-fed infants have more complex microbiota, with bifidobacteria, bacteroides, clostridia and streptococci all usually present. After weaning, a pattern of gut microbiota that resembles the adult pattern becomes established.
Mother's milk is recommended for all infants. However, in some cases breast feeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed. Infant formulae have been developed for these situations.
It has been proposed to add probiotics to infant formulae to encourage gut colonization to take place and to promote colonization with the “good” bacteria—lactobacilli—rather than the harmful bacteria—pathogens such as clostridia, etc. Typically a minimum of 107 cfu/g of formula is added although generally larger amounts are preferred, for example up to 1012 cfu/g of formula.
Another approach to promote the numbers and/or activities of beneficial bacteria in the colon is the addition of prebiotics to foodstuffs. A prebiotic is a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health. Such ingredients are non-digestible in the sense that they are not broken down and absorbed in the stomach or small intestine and thus pass intact to the colon where they are selectively fermented by the beneficial bacteria. Examples of prebiotics include certain oligosaccharides, such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS).
Human milk is known to contain a larger amount of indigestible oligosaccharides than most other animal milks. In fact, indigestible oligosaccharides represent the third largest solid component (after lactose and lipids) in breast milk, occurring at a concentration of 12-15 g/l in colostrum and 5-8 g/l in mature milk. Human milk oligosaccharides are very resistant to enzymatic hydrolysis, indicating that these oligosaccharides may display essential functions not directly related to their calorific value.
As the composition of human milk becomes better understood, it has also been proposed to add prebiotics to infant formula. Various infant formulas supplemented with prebiotics such as mixtures of fructooligosaccharides and galactooligosaccharides for example are commercially available. However, such mixtures approximate only roughly the mixture of oligosaccharides in human milk. Over 100 different oligosaccharide components have been detected in human milk some of which have not been so far detected in animal milks such as bovine milk at all or have been detected only in small quantities. Examples of classes of human milk oligosaccharide that are present in bovine milk and colostrum only in very small quantities or not at all are sialylated and fucosylated oligosaccharides.
Infant formulas containing both probiotics and prebiotics have also been proposed in the continual quest to produce infant formulas which replicate as closely as possible the composition and efficacy of human milk. For example, in WO 2005000748 it is proposed to supplement infant formula with a mixture of a Bifidobacterium breve strain, galactooligosaccharides and fructooligosaccharides (inulin). It is claimed that this mixture, which is described as a synbiotic, regulates the Bifidobacterium population in the colon of infants which consume the supplemented formula to a more “infant-like” population, that is, lower in Bifidobacterium catenulatum, Bifidobacterium pseudocatenulatum and Bifidobacterium adolescentis species and higher in Bifidobacterium infantis, Bifidobacterium breve and Bifidobacterium longum species. The mixture is also stated to be useful for the prevention or treatment of an immune condition.
However, a need remains for preparations comprising a probiotic and a prebiotic mixture specifically designed to enhance the efficiency and the efficacy of the probiotic.